载脂蛋白E基因多态性与冠心病的关系

目的 研究载脂蛋白E(ApoE)基因多态性与冠心病发病及对血脂代谢影响的关系。方法 对71例冠心病患者(CHD组)和69例正常对照者(对照组)的静脉全血白细胞提取DNA,应用PCR,HhaI酶切,用12％聚丙烯酰胺凝胶电泳,检测出其ApoE基因型及等位基因分布频率。结果 CHD组及对照组均检出4种基因型,分别是E     

冠心病患者血浆小而密低密度脂蛋白的分布特征

目的观察冠心病患者血浆低密度脂蛋白(lowdensitylipoprotein,LDL)亚组分的分布特征。方法采用密度梯度超速离心法分离24例冠心病患者和13例对照组血浆中脂蛋白的各亚组分:大而轻LDL(LDL1),中间LDL(LDL2),小而密LDL(LDL3,)的含量。结果①冠心病组与对照组在年龄、性别、身高、体重、总胆固醇、甘油三酯、高密度脂蛋白胆固醇(highdensitylipoproteincholesterol,HDL-C)、载脂蛋白A(apolipoproteinA,ApoA)和载脂蛋白B(apolipoproteinB,ApoB)和LDL等指标差异均无统计学意义(P>0.05);②冠心病组的亚组分LDL1的含量少,LDL3的含量多;对照组则相反,亚组分LDL1的含量多,LDL3的含量小;而且两组差异有统计学意义。而介于两者之间的亚组分LDL2的含量两组几乎一样。结论LDL3与冠心病的发生、发展有关;LDL3测定仍可作为预测冠心病危险性的指标之一,也是观察疗效的指标之一。     

Relationship of apolipoprotein E polymorphism with lipid profiles in atherosclerotic coronary artery disease

AimsThe aim was to determine the relationship between apolipoprotein E (ApoE) gene polymorphisms and lipid profile in patients with coronary artery diseases (CAD), and its role in the prediction of the severity of carotid and coronary atherosclerosis.Methods and resultsOne hundred patients were classified by coronary angiography: 80 patients with CAD and 20 controls (normal coronary angiography). Clinical data, carotid sonography, blood lipid profiles and ApoE genotyping (PCR-RFLP) were assessed. CAD patients had significantly increased plasma lipid profiles and carotid intimal-wall thickness (IMT) versus controls. In CAD patients; ApoE genotype frequencies were E3/E3 = 62.50%, E2/E3 = 18.75%, E3/E4 = 17.50%, E2/E4 = 1.25%, E4/E4 = 0 and E2/E2 = 0. But, E3/E4 genotype was significantly higher than controls (P < 0.05). Also, in CAD patients; ApoE allele frequencies were E3 = 80.6%, E2 = 10.0% and E4 = 9.4% but, ApoE4 alleles were associated with higher cholesterol (P = 0.034) and LDL-c (P = 0.003), while ApoE2 alleles were associated with higher triglycerides (P = 0.037) versus ApoE3 alleles. However, odds ratio of CAD patients had higher risk with E2/E3 genotypes (2.5-fold), E2 alleles (2.2-fold) and E4 alleles (2.1-fold). Moreover, CAD patients with ApoE4 alleles had significantly higher carotid IMT (1.23 ± 0.26 mm vs 0.97 ± 0.2 mm ApoE3, P = 0.006; however, non-significant vs 1.10 ± 0.40 mm ApoE2 and also, ApoE2 vs ApoE3 alleles, P = 0.633) and left anterior descending (LAD) coronary artery stenosis (vs ApoE3 alleles, P = 0.016).ConclusionIschemic patients with carotid and coronary atherosclerosis had significantly higher integration of dyslipidemia and ApoE alleles (ApoE2 with hypertriglyceridemia and ApoE4 with hypercholesterolemia and higher LDL-c). ApoE polymorphism may be an important diagnostic risk biomarker and may implicate therapeutic intervention in atherosclerotic ischemic patients.     

载脂蛋白E基因多态性对冠心病患者餐后甘油三酯代谢的影响

目的　探讨载脂蛋白 (Apo)E基因多态性对冠心病患者高脂餐后甘油三酯 (TG)代谢的影响。方法　 82例冠心病患者禁食 12h后接受高脂餐负荷试验。测定空腹和餐后 2、4、5、7h血清TG浓度。采用聚合酶链反应 (PCR)检测ApoE基因型。结果　 82例冠心病患者餐后 2、4、5、7h血清TG水平显著升高 (P <0 0 5 )。相关分析表明 :空腹TG水平与TG曲线下面积 (TG AUC)显著正相关 (r=0 4 36 ,P <0 0 5 )。ApoE 3/3(n =36 )、ApoE 3/4(n =2 5 )和ApoE2 /3(n =2 1)基因型患者的空腹血清TG水平差异无显著性。ε2和ε4携带者餐后血清TG水平以及TG AUC显著高于ε3/ε3携带者。结论　ApoE基因多态性影响冠心病患者餐后甘油三酯代谢。ε2和ε4等位基因与餐后富含甘油三酯脂蛋白代谢异常有关。     

老年人冠心病载脂蛋白E基因多态性的临床意义

目的：载脂蛋白Ｅ（ＡｏｏＥ）基因的多态性对老年冠心病发病的意义。方法：选择１００例老年冠心病患（ＣＨＤ组）及１００例键康。测定其血清血脂及脂蛋白「（ＬＰ（ａ）」。应用聚合酶链反应法（ＰＣＲ）,Ｈｈａｌ内切酶消化法确定ＡｏｏＥ基因多态性。结果：在冠心病组和对照组间ＡｏｏＥ基因频率及Ｅ２、Ｅ３、Ｅ４等位基因频率有显差异（Ｐ〈０．０５）;本组Ｅ４／３、Ｅ３／３基因组间比较,冠心病组ＴＣ、ＴＧ、Ａｏ     

Autoantibodies against oxidized low-density lipoprotein and cardiolipin in patients with coronary heart disease

Autoantibodies against oxidized low density lipoprotein (oxLDL) have been proposed to be independent predictors of atherosclerotic vascular disease. Because the levels of autoantibodies against oxLDL and cardiolipin might be modified by the presentation and severity of coronary heart disease (CHD), we measured their levels in patients with different manifestations of CHD (n=415, mean age 61 years, range 33 to 74 years) in a subset of the European Action on Secondary Prevention through Intervention to Reduce Events (EUROASPIRE) study. There were 109 patients with coronary artery bypass surgery, 106 patients with balloon angioplasty, 101 patients with acute myocardial infarction, and 99 patients with acute myocardial ischemia. Autoantibodies were measured by ELISA. Food records and fatty acid profiles of serum cholesteryl esters were used to evaluate dietary intake. Anti-oxLDL antibodies were significantly higher in the group with acute myocardial infarction than in other groups in men (coronary artery bypass surgery 1.91+/-1. 41, balloon angioplasty 2.11+/-2.19, acute myocardial infarction 2. 52+/-2.05, and acute myocardial ischemia 1.96+/-1.78; P=0.022, mean+/-SD) but not in women. The titers of anti-cardiolipin antibodies did not differ among the patient groups. Neither of the autoantibodies was associated with recurrent coronary events. Anti-oxLDL and anti-cardiolipin autoantibodies were not correlated with serum total cholesterol, high density lipoprotein cholesterol, or triglycerides, except that in women anti-oxLDL antibodies and triglycerides were positively correlated (r=0.225, P=0.011). In men, anti-cardiolipin antibodies were higher in the lowest quartiles of dietary intakes of vitamin E and polyunsaturated fat. Dietary intakes of vitamin E and polyunsaturated fat were correlated (r=0. 588, P<0.001). In conclusion, autoantibodies against oxLDL were associated with myocardial infarction in men. Anti-cardiolipin autoantibodies were inversely correlated with dietary intakes of vitamin E and polyunsaturated fat in men with CHD.     

冠心病患者载脂蛋白E基因型与血脂、脂蛋白水平的相关性

目的 :探讨冠心病 (CHD)患者载脂蛋白E(apoE)基因型与血脂、脂蛋白水平的相关性。 方法 :应用聚合酶链反应 限制性片段长度多态性法 (PCR RFLP) ,检测 119例CHD患者和 112例正常人 (对照组 )的apoE基因型 ;按常规方法测定血脂及脂蛋白水平。结果 :CHD组及对照组共检出 6种基因型 ,分别为 :ε2 /2、ε2 /3、ε3/3、ε3/4、ε4/4、ε2 /4 ;CHD组ε3/4基因型及ε4等位基因频率均显著高于对照组 (分别为P <0 .0 5 ,P <0 .0 1) ;CHD组ε2 /3、ε3/3、ε3/4基因型之间胆固醇 (TC)、低密度脂蛋白胆固醇 (LDL C)水平差异有显著性意义 (P <0 .0 5 )。结论 :apoE3/4基因型明显升高CHD患者TC、LDL C水平 ;apoE基因多态性可能通过影响血脂水平而影响CHD的发生     

载脂蛋白E基因多态性与冠心病关系的研究

目的：探讨载脂蛋白Ｅ（ａｐｏＥ）基因多态性在冠心病（ＣＨＤ）发生发展中的作用及其对血脂质、脂蛋白水平的影响。方法：应用聚合酶链反应技术和遗传学方法,测定９３ 例ＣＨＤ患者和９４例正常对照者的ａｐｏＥ基因型;按常规方法测定血浆脂质、脂蛋白水平。结果：共发现５ 种ａｐｏＥ基因型,分别为Ｅ３／３、Ｅ３／２、Ｅ４／３、Ｅ４／２和Ｅ４／４。ＣＨＤ组ａｐｏＥ４／３ 基因型和ε４ 等位基因频率及总胆固醇（ＴＣ）、低密度脂蛋白胆固醇（ＬＤＬ－Ｃ）均显著高于对照组（均Ｐ＜ ０．０１）,ａｐｏＡＩ的水平高于对照组（Ｐ＜ ０．０５）,其他血脂指标无显著性差异（ Ｐ＞ ０．０５）。在ＣＨＤ组各亚型之间,ＴＣ、ＬＤＬ－Ｃ和ａｐｏＡＩ水平之间存在显著性差异（Ｐ＜ ０．０５）。结论：ａｐｏＥε４ 等位基因是ＣＨＤ重要的遗传易患因素,ａｐｏＥ基因多态性亦影响血ＴＣ、ＬＤＬ－Ｃ和ａｐｏＡＩ水平。     

Low-density lipoprotein and apolipoprotein B: Clinical use in patients with coronary heart disease

Managing low-density lipoprotein (LDL) is an integral part of clinical practice. What remains controversial is whether we are using the best measure of LDL quantity for this purpose. Historically, the cholesterol content of LDL particles (LDLC) has been used to express LDL quantity. However, because of variability in the cholesterol carried in LDL particles, frequent disagreement occurs between LDLC and particle measures of LDL quantity, including apolipoprotein B-100 (apo B) or nuclear magnetic resonance (NMR) LDL particle number (LDL-P). Studies consistently demonstrate apo B and LDL-P are superior predictors of coronary heart disease (CHD) risk and superior indicators of low CHD risk on lipid-lowering therapy. Recent recommendations advocate that, in addition to LDLC and non-high-density lipoprotein cholesterol, apo B (or NMR LDL-P) be used as a target of therapy. This article reviews the rationale supporting these recommendations and provides a model for integrating LDL particle measures in clinical practice.     

载脂蛋白E基因多态性与冠心病相关因素的关联性

目的 :研究载脂蛋白 E基因多态性与冠心病的相关因素的关联性。方法 :测定 12 1例冠心病患者 （均经冠脉造影证实 ）的基因型。基因型的测定采用 PCR- REL P方法。冠状动脉狭窄诊断标准按 QCA方法确定。患者的血脂水平按常规方法测定。结果 :发现 5种基因型 ,分别为 E2 / 2、E2 / 3、E3/ 3、E3/ 4、E4 / 4。其中 ,E4等位基因型频率明显增高 （P<0 .0 5 ） ;与 E2 / 2 +E2 / 3比较 ,E3/ 3、E3/ 4 +E4 / 4基因型的患者冠状动脉多发狭窄比率偏高 ;狭窄程度偏重 （P<0 .0 5 ） ;E3/ 4 +E4 / 4等位基因型的冠心病携带者发病年龄偏小 （P<0 .0 5 ） ;E3/ 4 +E4 / 4组基因型的患者总胆固醇及低密度脂蛋白高于其他基因型 （P<0 .0 1）。结论 :载脂蛋白 E基因多态性与冠心病早发、严重度和血脂水平相关。     

不同类型心绞痛患者低密度脂蛋白及氧化型低密度脂蛋白的比较研究

目的探讨血浆低密度脂蛋白胆固醇（LDL-C）和氧化型低密度脂蛋白（ox-LDL）与冠状动脉粥样硬化病变严重程度的关系。方法病例选择：冠状动脉痉挛组（CAS,n=31）,临床上具有胸痛表现、冠状动脉造影无显著狭窄并经过乙酰胆碱试验确诊的患者,根据痉挛血管形态分为节段性痉挛组和弥漫性痉挛组;稳定性心绞痛组（SAP,n=35）,为稳定的劳力型心绞痛患者,根据冠状动脉造影结果分为单支病变组和多支病变组;对照组（n=24）,为健康体检患者。各组于清晨空腹采取静脉血,采用全自动生化分析仪测定血浆LDL-C,用ELISA法检测血浆ox-LDL含量,分组比较其LDL．C及ox-LDL水平。结果血浆LDL-C水平SAP亚组[单支病变组（2．6±0．9）mmol／L,多支病变组（2．8±0．9）mmol／L]和CAS亚组[弥漫性痉挛组（3．2±0．5）mmol／L,节段性痉挛组（2．9±0．8）mmol／L]间差异无统计学意义,但均高于对照组[（2．2±0．5）mmol／L,P〈0．05];SAP组血浆ox-LDL含量[（575±219）μg/L]高于对照组[（218±35）μg/L,P〈0．01]和CAS组[（299±117）μg/L,P〈0．01],CAS组与对照组比较,差异无统计学意义（P〉0．05）;弥漫性痉挛组[（225±63）μg／L]、节段性痉挛组[（328±123）μg／L]、单支血管病组[（462±72）μg／L]、多支血管病变组[（672±92）μg／L]的血浆ox—LDL浓度逐步上升,各组间差异有统计学意义（P〈0．05）,与冠状动脉硬化程度呈一致趋势,而血浆LDL水平组间差异无统计学意义。结论血浆ox-LDL比LDL—C更能准确地预测冠状动脉粥样硬化的严重程度,调脂治疗应该更为重视降低ox-LDL,而不应单纯控制LDL水平。     

Association of low-density lipoprotein particle size and ratio of different lipoproteins and apolipoproteins with coronary heart disease

BACKGROUND: Worldwide coronary heart disease (CHD) is estimated to be the leading cause of death. Current knowledge about prevention of CHD is mainly derived from developed countries. Therefore, this study aimed to find out the association of CHD with ratios of different lipoproteins and apolipoproteins, LDL particle size, as well as different traditional risk factors in Asian Indian population in Eastern part of India. METHODS: Case-control study of 100 patients with CHD and 98 healthy controls were age and sex matched. After clinical evaluation, blood samples were collected for biochemical assays. RESULTS: Multivariate logistic regression analysis found apoB (OR 2.96; 95% CI 1.02-8.54), apoB/HDL-c (OR 4.14; 95% CI 1.33-12.83), nonHDL-c (OR 5.41; 95% CI 2.08-14.10), apoB/apoAI (OR 6.64; 95% CI 2.37-18.57), and LDL particle size (9.59; 95% CI 2.92-31.54) were independently associated with CHD. Area under the ROC curves derived from the model (AUROC 0.947; 95% CI 0.916-0.977) are significantly higher than any other variables. CONCLUSIONS: Findings from the multivariate analysis, apoB, apoB/HDL-c, nonHDL-c, apoB/apoAI, and LDL particle size are potent indicators and useful for diagnosis of predisposed CHD.     

Effects of atorvastatin on oxidized low-density lipoprotein, low-density lipoprotein subfraction distribution, and remnant lipoprotein in patients with mixed hyperlipoproteinemia

Atorvastatin (10 to 20 mg/day) was administered for 3 months to 15 outpatients (average age 58 +/- 4 years) with hypercholesterolemia accompanied by hypertriglyceridemia without hypolipemic treatment. Changes in lipid profile, particularly oxidized low-density lipoprotein (LDL) (malondialdehyde LDL), subfractions of LDL, and remnant lipoprotein (RLP) cholesterol, were examined before and after administration. In addition, the influence of atorvastatin on lipoprotein(a) (known to be an independent risk factor for atherosclerosis), asymmetric dimethylarginine (known to be an endogenous inhibitor of nitric oxide synthase), and homocysteine (methionine metabolite) was also investigated. Administration of atorvastatin significantly decreased serum total cholesterol, LDL cholesterol, and triglycerides. Conversely, a significant increase in high-density lipoprotein cholesterol was shown. In LDL subfractions, large, buoyant LDL fractions were not influenced by treatment with atorvastatin (before administration, 99 +/- 14 mg/dl; after administration, 91 +/- 6 mg/dl, shown as a cholesterol content in each subfraction), but a marked decrease in small, dense LDL fractions (p <0.001) (before administration, 119 +/- 17 mg/dl; after administration, 43 +/- 10 mg/dl) was shown. Moreover, oxidized LDL was significantly decreased (p < 0.01) (before administration, 169 +/- 13 U/L; after administration, 119 +/- 10 U/L) and RLP cholesterol also was significantly decreased (p <0.01) (before administration, 11.9 +/- 2.0 mg/dl; after administration, 6.0 +/- 0.9 mg/dl) with atorvastatin treatment. No significant change was observed in fasting plasma glucose, hemoglobin A1c, lipoprotein(a), asymmetric dimethylarginine, homocysteine, and so on. These data suggest that administration of relatively low doses of atorvastatin to patients with hypercholesterolemia accompanied with hypertriglyceridemia results in a decrease not only in LDL cholesterol and triglycerides, but also in oxidized LDL and RLP cholesterol, with an increase in high-density lipoprotein cholesterol. Furthermore, small, dense LDL decreased with a shift in LDL subfractions to large, buoyant fractions, and these changes are considered to be involved in the inhibition of the onset and progression of atherosclerosis.     

Correlation study between lipoprotein subfraction and different onset age of coronary heart disease

正Objective To clarify correlation between lipoprotein subfraction and different age of coronary heart disease.Methods A total of 1 217 patients with coronary angiography(CAG)confirmed by CAD were consecutively enrolled.According to onset age,the patients were divided into 3 groups:very early CAD group,n=135     

冠心病患者血浆小、密低密度脂蛋白的测定及其临床意义

目的观察冠心病患者血浆小、密低密度脂蛋白(sdLDL)和脂类成分的变化及相互关系。方法采用2％～16％非变性聚丙烯酰胺梯度胶电泳和凝胶成像分析,测定105例冠心病患者和76例健康对照者血浆sdLDL．同时测定血脂。结果sdLDL>50％的检出率,冠心病组为38．1％,对照组为10．5％(P<0．001);sdLDL增多患者的甘油三酯(TG)水平[(2．42±1．24)mmol／L]明显高于sdLDL正常者[(1．48±0．64)mmol／L](P<0．001)。结论sdLDL与冠心病发生发展有关,且与TG关系密切;sdLDL测定可作为预测冠心病危险性的指标之一。     

冠心病家族史大学生apo E基因多态性的临床研究

目的:探讨大学生载脂蛋白E(apoE)基因多态性,及其对血脂代谢紊乱、动脉粥样硬化(AS)和冠心病(CHD)的影响。方法:对广东地区高校152名健康汉族大学生,在问卷调查的基础上,根据一、二级亲属有无CHD病史分为阳性组与对照组,采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法进行apoE基因分析。结果:有CHD家族史的阳性组e_4等位基因频率显著高于无CHD家族史的阴性组(P<0.05)。结论:apoE基因多态性与AS、CHD易感性密切有关,e_4可能是CHD的重要遗传因子。     

载脂蛋白H基因多态性与冠心病及血脂代谢关系的研究

目的探讨载脂蛋白H(ApoH)外显子3、8基因多态性与冠心病(CHD)、血脂代谢的关系。方法采用聚合酶链式反应-单链构象多态技术(PCR-SSCP)分析方法,分析了100例健康人及110例CHD患者的ApoH外显子3,8基因型及血脂测定。结果(1)CHD组外显3 GG基因型的频率为81.8%,GA+AA基因型频率为18.2%,G等位基因频率为88%,A等位基因频率是12%,与对照组比较无差异。(2)CHD组外显子8 GG基因型频率为74.5%,GC基因型频率为25.5%,G等位基因频率为87%,C等位基因频率为13%,与对照组比较CHD组的GC基因型频率及C等位基因频率显著增高。(3)外显子3 CHD组低密度胆固醇(LDL-C)高于对照组(P<0.05),CHD组及对照组各基因型间的血脂水平无差异;(4)外显子8 CHD组LDL-C也显著高于对照组(P<0.05),CHD组GC基因型的甘油三酯(TG)显著高于GG型和及对照组的各基因型。结论(1)ApoH外显子3基因多态性与CHD及血脂代谢无相关性;(2)ApoH外显子8 GC基因型及C等位基因与CHD有关,ApoH外显子8基因多态性与TG有关。     

冠心病家族史大学生apo E基因多态性的临床研究

目的探讨大学生载脂蛋白E(apo E)基因多态性,及其对血脂代谢紊乱、动脉粥样硬化(AS)和冠心病(CHD)的影响.方法对广东地区高校152名健康汉族大学生,在问卷调查的基础上,根据一、二级亲属有无CHD病史分为阳性组与对照组,采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法进行apo E基因分析.结果有CHD家族史的阳性组e4等位基因频率显著高于无CHD家族史的阴性组(P＜0.05).结论apo E基因多态性与AS、CHD易感性密切有关,e4可能是CHD的重要遗传因子.